Ceramide-activated protein kinases A and C zeta inhibit kidney proximal tubule cell Na(+)-ATPase.

The basolateral membranes of kidney proximal tubule cells have (Na(+)+K(+))-ATPase and Na(+)-ATPase activities, involved in Na(+) reabsorption. We showed that ceramide (Cer) modulates protein kinase A and protein kinase C which are involved in regulating ion transporters. Here we show that ceramide, promotes 60% inhibition of Na(+)-ATPase activity (I(50) approximately 100nM). This effect was completely reversed by inhibiting but did not involve the classic signaling pathway. In these membranes we found the Cer-activated atypical duanyu1531 zeta isoform. When is inhibited, Cer ceases to inhibit the Na(+)-ATPase, allowing the signaling pathway to recover its stimulatory effect on the pump. There were no effects on the (Na(+)+K(+))-ATPase. These results reveal Cer as a potent physiological modulator of the Na(+)-ATPase, participating in a regulatory network in kidney cells and counteracting the stimulatory effect of duanyu1529 via

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